PROJECT ABSTRACT This application represents the fourth competitive renewal (years 21-25) for our T32 Program ?Training in Age-related Neurodegenerative Diseases?. The program supports 6 predoctoral and 4 postdoctoral trainees per year. The program is based at the Perelman School of Medicine, School of Arts and Sciences, School of Dental Medicine at The University of Pennsylvania, and the Children?s Hospital of Philadelphia. Together, these institutions have one of the largest programs on neurodegenerative disease research in the country, with a funded base of >$20 million as determined by federal, pharmaceutical and foundation grants held by the trainers. Among the many individuals who study neurodegenerative diseases on our campus, a select group of 22 mentors are associated with this T32 program. In our program, we place specific emphasis on collaborative science and a commitment to training students and postdoctoral fellows: all trainers have published numerous papers with other trainers, 12 of the trainers share jointly funded NIH grants with other trainers, 20 of our trainees have published with 2 or more trainers, there are many joint lab meetings, and our trainers participate in extensive programmatic activities and minority-recruitment efforts. Over the past 20 years, the program has supported 36 predoctoral trainees working in 24 different laboratories. Currently, 1 is an associate professor, 6 are assistant professors of which 3 are working on age-related neurodegenerative diseases, 1 is an instructor, 2 are postdocs, and 9 are doing residency and/or research fellowships at distinguished universities such as Harvard, Penn, Washington University, Johns Hopkins, and UCSF. Two are in private practice, 2 others are managing non-profit foundations, one is an academic biostatistician, one is a freelance science writer and another is a manager of research services. Three completed their PhDs and are in the process of completing their MDs, 6 are still in training. Our training program also supported 27 postdocs over the past 20 years working in 16 different laboratories. Currently 3 are professors, 2 are associate professors, 3 are assistant professors, 1 is a research associate,1 is an instructor, 1 is a lecturer, 1 is in private practice, 4 work in the pharmaceutical industry, 1 is a senior consultant in pharmaceutical industry, 1 is a program director at NIDDK, NIH, and 5 are still in training. Many of the predoctoral and postdoctoral trainees are stepping into leadership roles?one is the Founder and CEO of Avid Radiopharmaceuticals and a senior vice-president of clinical and product development at Eli Lilly; another is the chair of Department of Neurobiology and Behavior, University of California, Irvine; and a third is the Director of a Translational Neurotrauma Research Program at the University of Arizona. Many have established their own laboratories with independent grant support from the NIH. Thus, based on these outcomes, we feel that we are training young scientists effectively, and we propose to maintain the training program at the present size.